The DOI matches its Crossref record; 14 of the 14 references it cites were found in a registry or an index.
Runx1 is required for zebrafish blood and vessel development and expression of a human RUNX1-CBF2T1 transgene advances a model for studies of leukemogenesis
Abstract
RUNX1/AML1/CBFA2 is essential for definitive hematopoiesis, and chromosomal translocations affecting RUNX1 are frequently involved in human leukemias. Consequently, the normal function of RUNX1 and its involvement in leukemogenesis remain subject to intensive research. To further elucidate the role of RUNX1 in hematopoiesis, we cloned the zebrafish ortholog (runx1) and analyzed its function using this model system. Zebrafish runx1 is expressed in hematopoietic and neuronal cells during early embryogenesis. runx1 expression in the lateral plate mesoderm co-localizes with the hematopoietic transcription factor scl, and expression of runx1 is markedly reduced in the zebrafish mutants spadetail and cloche. Transient expression of runx1 in cloche embryos resulted in partial rescue of the hematopoietic defect. Depletion of Runx1 with antisense morpholino oligonucleotides abrogated the development of both blood and vessels, as demonstrated by loss of circulation, incomplete development of vasculature and the accumulation of immature hematopoietic precursors. The block in definitive hematopoiesis is similar to that observed in Runx1 knockout mice, implying that zebrafish Runx1 has a function equivalent to that in mammals. Our data suggest that zebrafish Runx1 functions in both blood and vessel development at the hemangioblast level, and contributes to both primitive and definitive hematopoiesis. Depletion of Runx1 also caused aberrant axonogenesis and abnormal distribution of Rohon-Beard cells, providing the first functional evidence of a role for vertebrate Runx1 in neuropoiesis. To provide a base for examining the role of Runx1 in leukemogenesis, we investigated the effects of transient expression of a human RUNX1-CBF2T1 transgene [product of the t(8;21) translocation in acute myeloid leukemia] in zebrafish embryos. Expression of RUNX1-CBF2T1 caused disruption of normal hematopoiesis, aberrant circulation, internal hemorrhages and cellular dysplasia. These defects reproduce those observed in Runx1-depleted zebrafish embryos and RUNX1-CBF2T1 knock-in mice. The phenotype obtained with transient expression of RUNX1-CBF2T1 validates the zebrafish as a model system to study t(8;21)-mediated leukemogenesis.
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Cites
Wang, Q., Stacy, T., Binder, M., Marin-Padilla, M., Sharpe, A. H., & Speck, N. A. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.8.3444 · Cited by 1,178
Song, W.-J., Sullivan, M. G., Legare, R. D., Hutchings, S., Tan, X., Kufrin, D., Ratajczak, J., Resende, I. C., Haworth, C., Hock, R., et al. (1999) · Nature Genetics · doi:10.1038/13793 · Cited by 1,100
Miyoshi, H., Shimizu, K., Kozu, T., Maseki, N., Kaneko, Y., & Ohki, M. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.23.10431 · Cited by 872
Cbfa2 is required for the formation of intra-aortic hematopoietic clusters
North, T., Gu, T.-L., Stacy, T., Wang, Q., Howard, L., Binder, M., Marín-Padilla, M., & Speck, N. A. (1999) · Development · doi:10.1242/dev.126.11.2563 · Cited by 662
Erickson, P., Gao, J., Chang, K., Look, T., Whisenant, E., Raimondi, S., Lasher, R., Trujillo, J., Rowley, J., & Drabkin, H. (1992) · Blood · doi:10.1182/blood.v80.7.1825.1825 · Cited by 631
Ogawa, E., Maruyama, M., Kagoshima, H., Inuzuka, M., Lu, J., Satake, M., Shigesada, K., & Ito, Y. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.14.6859 · Cited by 608
The transcriptional control of hematopoiesis [see comments]
Shivdasani, R., & Orkin, S. (1996) · Blood · doi:10.1182/blood.v87.10.4025.bloodjournal87104025 · Cited by 560
Ogawa, E., Inuzuka, M., Maruyama, M., Satake, M., Naito-Fujimoto, M., Ito, Y., & Shigesada, K. (1993) · Virology · doi:10.1006/viro.1993.1262 · Cited by 493
AML1–ETO downregulates the granulocytic differentiation factor C/EBPα in t(8;21) myeloid leukemia
Pabst, T., Mueller, B. U., Harakawa, N., Schoch, C., Haferlach, T., Behre, G., Hiddemann, W., Zhang, D.-E., & Tenen, D. G. (2001) · Nature Medicine · doi:10.1038/86515 · Cited by 463
Yergeau, D. A., Hetherington, C. J., Wang, Q., Zhang, P., Sharpe, A. H., Binder, M., Marín-Padilla, M., Tenen, D. G., Speck, N. A., & Zhang, D.-E. (1997) · Nature Genetics · doi:10.1038/ng0397-303 · Cited by 346
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Traver, D., Paw, B. H., Poss, K. D., Penberthy, W. T., Lin, S., & Zon, L. I. (2003) · Nature Immunology · doi:10.1038/ni1007 · Cited by 800
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Davidson, A. J., & Zon, L. I. (2004) · Oncogene · doi:10.1038/sj.onc.1207943 · Cited by 419
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Rhodes, J., Hagen, A., Hsu, K., Deng, M., Liu, T. X., Look, A. T., & Kanki, J. P. (2005) · Developmental Cell · doi:10.1016/j.devcel.2004.11.014 · Cited by 353
RUNX1 and GATA-1 coexpression and cooperation in megakaryocytic differentiation.
Elagib, K. E., Racke, F. K., Mogass, M., Khetawat, R., Delehanty, L. L., & Goldfarb, A. N. (2003) · Blood · doi:10.1182/blood-2002-09-2708 · Cited by 332
Coffman, J. A. (2003) · Cell Biology International · doi:10.1016/s1065-6995(03)00018-0 · Cited by 204
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Runx1 is involved in primitive erythropoiesis in the mouse
Yokomizo, T., Hasegawa, K., Ishitobi, H., Osato, M., Ema, M., Ito, Y., Yamamoto, M., & Takahashi, S. (2008) · Blood · doi:10.1182/blood-2007-05-091637 · Cited by 78
Imamura, S., Uchiyama, J., Koshimizu, E., Hanai, J.-I., Raftopoulou, C., Murphey, R. D., Bayliss, P. E., Imai, Y., Burns, C. E., Masutomi, K., et al. (2008) · PLoS ONE · doi:10.1371/journal.pone.0003364 · Cited by 58
Using the Zebrafish as a Genetic Model to Study Erythropoiesis
Zhang, Y., Chen, M., & Chen, C. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms221910475 · Cited by 25
Metadata
- Authors
- Kalev-Zylinska, M. L., Horsfield, J. A., Flores, M. V. C., Postlethwait, J. H., Vitas, M. R., Baas, A. M., Crosier, P. S., & Crosier, K. E.
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2002-04-15
- Volume
- 129
- Issue
- 8
- Pages
- 2015-2030
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- OpenAlex
- W2128483455
- Cited by
- 289
- References
- 14
- FWCI
- 5.14
- Type
- journal article
- Language
- en
- Open access
- closed
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